Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1

Genesis. 2012 Feb;50(2):112-8. doi: 10.1002/dvg.20798. Epub 2012 Jan 6.

Abstract

The Notch1 receptor plays a critical role in cell fate decisions during development. Activation of Notch signaling has been implicated in several types of cancer, particularly T-cell acute lymphoblastic leukemia (T-ALL). Consequently, several transgenic mouse strains have been made to study the role of Notch1 in T-ALL. However, the existing Notch1 transgenic lines mimic a translocation event found in only ∼1% of T-ALL cases. Here we describe three novel NOTCH1 transgenic mouse strains that have Cre-inducible expression of the entire human NOTCH1 locus, each possessing a common mutation found in T-ALL. Unlike existing Notch1 transgenic strains, these NOTCH1 transgenic strains express full-length receptors from an endogenous human promoter that should be susceptible to a number of Notch antagonists that have recently been developed. These strains will allow researchers to modulate Notch signaling to study both normal development and cancer biology.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Transgenic*
  • Mutation
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / metabolism
  • Signal Transduction

Substances

  • NOTCH1 protein, human
  • Receptor, Notch1